Persistent effects on blood pressure and renal haemodynamics following chronic angiotensin converting enzyme inhibition with perindopril

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats aged 4 and 16 weeks were given an acute oral dose of either Perindopril (3 mg/kg) or vehicle. Direct blood pressure (BP), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, and renal vascular resistance (RVR) calculated. GFR and RBF were lower in vehicle-treated SHR than WKY at 4 weeks of age, but were not different at 16 weeks. Acute Perindopril increased GFR and RBF and reduced RVR in both strains at both 4 and 16 weeks. Total body sodium, sodium intake and blood pressure were measured in SHR and WKY from 1 to 28 weeks of age. Rats of both strains were treated daily between 4 and 16 weeks of age with either Perindopril (3 mg/kg per day) or vehicle. Chronic Perindopril treatment prevented the development of hypertension in the SHR. From 16 to 28 weeks of age, after stopping Perindopril, BP rose slowly in SHR, but remained lower than vehicle-treated SHR. No changes in total body sodium occurred during Perindopril treatment. GFR and RBF were measured in SHR and WKY chronically treated with either Perindopril or vehicle, 3 days or 12 weeks after stopping treatment. In WKY, GFR and RBF were not different between Perindopril-treated and untreated rats at either measurement. In SHR, GFR and RBF remained significantly higher in rats previously treated with Perindopril at both ages. These findings suggest that renal haemodynamic abnormalities may be important in the initiation of hypertension in the SHR. These renal circulatory abnormalities and the hypertension of the SHR depend, at least in part, on intact converting enzyme activity, yet appear to be independent of abnormalities of total body sodium. At a later age, hypertension seems to develop independently of renal vascular abnormalities.     

Effects of once-daily osmotic-release methylphenidate on blood pressure and heart rate in children with attention-deficit/hyperactivity disorder: results from a one-year follow-up study

OBJECTIVE: Studies of vital signs in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) receiving stimulants indicate a variable effect on blood pressure (BP) and heart rate (HR). We evaluated the longer-term effects on vital signs of once-daily osmotic-release methylphenidate (MPH, Concerta) in children with ADHD. METHODS: As part of a 1-year open-extension trial, we studied children with ADHD (aged 6-13 years; baseline assessment, n = 432) who were entered into an open-label study of osmotic-release MPH (18-54 mg) for up to 1 year. Subjects' BP and HR were recorded at monthly visits and, when applicable, analyses were by last observation carried forward. RESULTS: Compared to off-drug baseline, osmotic-release MPH was associated with minor clinical, although statistically significant, changes in systolic and diastolic blood pressure (DBP) (3.3 and 1.5 mm Hg, Ps < 0.001) and HR (3.9 bpm, P < 0.0001) at 12-month end point. There was no clear dose-response relationship. There was no tolerance to the pressor effects of osmotic-release MPH over the 1-year period. There was an inverse relationship between baseline vital signs and positive change in vital signs at end point. CONCLUSIONS: Over a 12-month period, osmotic-release MPH produced minor clinical, although statistically significant, changes in BP and HR in children with ADHD.     

Alpha-adrenoceptor blockade in patients with mild to moderate hypertension: long-term renal effects of doxazosin.

Using constant infusion technique and a water-loading procedure, we investigated renal hemodynamic and excretional variables in 15 essential hypertensive patients [diastolic blood pressure (DBP) 102 +/- 10 mm Hg] after 3 weeks of placebo and after 16 weeks of treatment with a postjunctional alpha 1-adrenoceptor-antagonist, doxazosin (1-16 mg) once daily. A minor decrease in supine DBP (p less than 0.05) but no significant changes in systolic BP (SBP) and heart rate (HR) were observed. No significant changes were noted in glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR). The mean renal excretion rate of sodium, potassium, uric acid, and albumin for the entire group was unaffected by the treatment, but the individual changes in sodium clearance correlated significantly with changes in mean BP (r = 0.64, n = 15, p less than 0.05). Six patients showed an increase in sodium excretion after treatment, whereas nine showed a decrease. No decrease in mean body weight was noted, but the BP reduction after 5 months of treatment correlated significantly with the changes in body weight (r = 0.62, n = 15, p less than 0.01). The results indicate that long-term treatment with doxazosin had no deleterious effect on renal function, but the effects on BP were rather modest. The individual BP response is probably determined by the degree of fluid retention even if an intact pressure-natriuresis relationship could still be demonstrated during chronic therapy.     

Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression

BACKGROUND: Thyrotropin-releasing hormone (TRH) is a tripeptide that produces endocrine and behavioral effects in animals and humans. Some studies have shown transient antidepressant activity after morning administration of TRH. We hypothesized that nocturnal administration of TRH, when the circadian sensitivity of the TRH receptor is at its peak, may result in a more robust antidepressant effect. METHODS: Twenty patients with bipolar (BP) type I or BP type II major depressive episode (MDE) were given nocturnal intravenous TRH 500 microg (n = 10) or saline (n = 10) at midnight in a randomized, double-blind fashion. Antidepressant activity was assessed using the Hamilton Depression Rating (HAM-D), Young Mania Rating (YMR), and Profile of Mood (POMS) scales over a 48-hour period. Thyrotropin (TSH), total T4, and free T3 concentrations were measured before and after TRH administration. Data were analyzed using chi test, Fisher exact test, and repeated-measures ANOVA. RESULTS: Sixty percent of the TRH group and 10% of the saline group showed a > or =50% reduction in baseline total HAM-D score within 24 hours (P = 0.03). HAM-D ratings fell by an average of 52% after TRH administration versus 12% after saline administration (P = 0.038). There was a modest increase in YMR scores after TRH compared with saline (P < 0.032). No manic or hypomanic episodes were observed. Antidepressant effects of TRH lasted up to 48 hours. There was no correlation between DeltaTSH, DeltaT4, or DeltaT3 measures after TRH (or saline) administration and the change in HAM-D scores. CONCLUSIONS: Nocturnal TRH administration may produce a rapid antidepressant effect in some patients with BP I and BP II MDE.     

Renal effects of bunazosin, a new alpha 1-adrenoceptor blocker, in patients with mild-to-moderate essential hypertension.

Renal effects of 4-week fixed maintenance doses of bunazosin three times daily (2.0 mg t.i.d., n = 8) and propranolol (40 mg t.i.d., n = 8) were evaluated in patients with mild-to-moderate essential hypertension [World Health Organization (WHO) stages I and II]. Both bunazosin and propranolol decreased blood pressure (BP) significantly (p less than 0.05), but the magnitude of reduction in diastolic BP (DBP) was greater with bunazosin (p less than 0.05) than with propranolol. Bunazosin produced a nonsignificant increase in renal blood flow (RBF) by 14%, a significant increase in glomerular filtration rate (GFR) 11% (p less than 0.05), and a decrease in total renal vascular resistance (TRR) by 15% (p less than 0.05), whereas propranolol caused no significant changes in these parameters. Urinary sodium excretion rate and the fractional excretion of sodium were unchanged by either of the drugs. The results of this short-term study suggest that bunazosin may be a drug that will increase RBF and GFR and decrease TRR with a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. Whether these renal functional effects of the drug would benefit such patients must be determined in long-term studies.     

吡格列酮对2型糖尿病患者血压超敏C反应蛋白和肾功能的影响

目的 观察吡格列酮对2型糖尿病患者血压、超敏C反应蛋白和肾功能的影响.方法 72例24h尿白蛋白排泄量(UAE)在30-300mg的2型糖尿病患者在常规降糖治疗的同时随机分为治疗组(吡格列酮30mg/d)36例和对照组36例,疗程24周,分别观察治疗前后2组空腹血糖( FBS)、餐后2h血糖(2h PBG)、糖化血红蛋...     

Lisinopril in paediatric medicine: a retrospective chart review of long-term treatment in children.

OBJECTIVE: To investigate the antihypertensive efficacy, dosing, tolerability and effects on growth of lisinopril (off label-use) in paediatric patients during long-term treatment. DESIGN: We conducted a retrospective analysis of data from 123 patients treated with lisinopril in a paediatric nephrology clinic over a 9.3-year period. Patients were categorised by age group and predominant clinical diagnosis: hypertension (n=59), renal parenchymal disease (n=27), diabetes mellitus (n=33) and miscellaneous (n=4). RESULTS: The vast majority were Caucasian (93%) and boys (66%). Mean duration of treatment was 2.0 years. Age at start of treatment ranged from two months to 17.7 years. Mean lisinopril starting and final doses were 0.105 mg/kg/day for hypertensive patients and 0.108 mg/kg/day for patients with renal disease, respectively. The most common adverse event was hypotension (8.6% of the patients). Haematology and serum biochemistry profiles were unaffected by lisinopril. Growth was not different from data recorded by Belgian population studies. In 29 of the 47 hypertensive patients who received lisinopril monotherapy, comparing blood pressure (BP) at baseline and after six months treatment, mean reductions in systolic/diastolic BP were 19/18 mmHg. CONCLUSIONS: Lisinopril was well tolerated in paediatric patients. Doses of 0.1 mg/kg/day produced clinically significant BP reduction in hypertensive patients.     

Effects of ACE inhibition and angiotensin II receptor blockade on glomerular basement membrane protein excretion and charge selectivity in type 2 diabetic patients.

Angiotensin-converting enzyme (ACE) inhibitors may reduce urinary albumin excretion (UAE) by decreasing glomerular pressure and increasing glomerular charge selectivity through preservation of glycosaminoglycans. The effect of Angiotensin II antagonism on glomerular charge selectivity remains to be determined. The aim of this study was to compare the effects of an AT1 blocker losartan and an ACE inhibitor (ACE-I) enalapril on UAE, extracellular matrix proteins, glycosaminoglycan excretion (UGAG) and red blood cell anionic charge (RBCCh) which are the indirect markers of glomerular basement membrane anionic content in hypertensive Type 2 diabetic patients. Twenty-four patients were randomised into two groups and received either enalapril (520 mg/d) or losartan (50100 mg/d). All parameters were measured at baseline and after six months of treatment. At the end of six months, systolic and diastolic blood pressures (BP), UAE rates, UGAG excretion and RBCCh were significantly and equally reduced in both treatment groups compared with baseline. RBCCh was negatively correlated with UAE (r=-0.57, p<0.0001) and UGAG excretion (r=-0.57, p<0.0001); UAE was correlated with UGAG excretion (r=0.58, p<0.0001). In conclusion, enalapril and losartan treatment were equally effective in reducing BP, UAE as well as UGAG excretion and preserving RBCCh in hypertensive Type 2 diabetic patients. ACE inhibition and AT1-receptor blockade may have favourable effects on preserving glomerular anionic content in hypertensive diabetic patients.     

Effect of long-term tacrolimus immunosuppression on renal function in liver transplant recipients

STUDY OBJECTIVES: To describe changes in renal function occurring after long-term treatment with tacrolimus in clinically stable liver transplant recipients, and to identify risk factors for a clinically significant decline in renal function in these patients. DESIGN: Retrospective cohort study. Setting. University medical center. Patients. Four hundred thirty-two patients aged 18 years or older who underwent liver transplantation between January 1, 1996, and December 31, 2000, and received tacrolimus as part of their immunosuppressive treatment regimen. MEASUREMENTS AND MAIN RESULTS: Six hundred patients were identified from an electronic records review. Those who received multiorgan transplants, were not receiving their first liver transplant, or died during the hospitalization were excluded from the study. Outcomes measured were change in mean glomerular filtration rate (GFR) up to 5 years after transplantation, and proportion of patients with a decline in GFR of 30% or greater from baseline to the last recorded serum creatinine level. Covariates that affected this decline were identified using a logistic regression model. Patients were followed for a mean +/- SD of 3.7 +/- 2.0 years. Mean GFR showed a statistically significant decline from baseline to end of follow-up (67.7 +/- 25.6 vs 58.4 +/- 26.5 ml/min/1.73 m(2), p<0.001). The GFR declined by 30% or more in 154 (35.6%) patients. Increasing age (odds ratio [OR] = 1.03, p=0.020), female sex (OR = 1.92, p=0.006), higher baseline GFR (OR = 1.03, p<0.001), and diagnosis of diabetes mellitus (OR = 1.74, p=0.059) were identified as predictors of this outcome. CONCLUSION: After the acute posttransplantation period, liver transplant recipients given long-term treatment with tacrolimus experienced only small changes in GFR over time. Patients with diabetes and women had the highest risk of experiencing a clinically significant decline in renal function.     

A comparative study of lisinopril and atenolol on low degree urinary albumin excretion,renal function and haemodynamics in uncomplicated,primary hypertension

Summary The presence of slightly increased urinary albumin excretion (UAE), even at levels well below levels detectable by an ordinary dipstick, has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability.The aim of the present investigation was to study the effects of two different antihypertensive drug regimens, an ACE inhibitor and a-adrenoceptor antagonist, on the low UAE rate observed in subjects with uncomplicated, mild to moderate primary hypertension.After a 4-week placebo run-in period, 49 patients (mean age 54 y) were randomly assigned in a double blind manner either to further 4 weeks on placebo (P,n =15), 8 weeks on lisinopril (L,n = 17; 20 mg/40 mg o. d.) or 8 weeks on atenolol (A,n =17; 50 mg/100 mg o. d.). The 24-h UAE was measured every second week. At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured.Both drugs lowered blood pressure (BP) to a similar extent after 4 and 8 weeks of treatment; the blood pressures were 160/106 (P), 159/104 (L) and 154/103 (A) at entry, and 133/83 (L) and 134/87 (A) at the end of the study after 8 weeks. On entry the 24-h UAE in all patients ranged from 4 to 49 mg (mean 14.1 mg), and it did not differ significantly between groups. After 4 weeks the UAE during 24 h was reduced by approximately one third in the lisinopril-treated group, and by 10 % in the atenolol reated group, whereas it remained unaltered in the group on placebo. After 8 weeks the 24-hour UAE was approximately 20 % lower compared to baseline levels in the lisinopril-treated patients. In the atenolol-treated group the UAE was unaltered compared to baseline. However, none of the changes in the UAE was statistically significant, nor were there any statistically significant differences between the two antihypertensive regimens. Moreover, there were no significant effect of the lisinopril or atenolol treatment on renal function or on renal haemodynamics.It is concluded that in patients with uncomplicated, mild to moderate hypertension both an ACE-inhibitor, such as lisinopril, as well as a ₁-selective adrenoceptor blocking agent, such as ate     

Plasma matrix metalloproteinase-9 and ACE-inhibitor-induced improvement of urinary albumin excretion in non-diabetic, microalbuminuric subjects.

INTRODUCTION: Elevated plasma matrix metalloproteinase-9 (MMP-9) levels have been suggested to precede the development of microalbuminuria. As angiotensin-converting enzyme (ACE) inhibitors effectively reduce urinary albumin excretion (UAE), in the present study we have investigated the potential association of plasma MMP-9 levels with UAE and treatment effects of ACE-inhibition. MATERIAL AND METHODS: In a placebo-controlled randomised trial we determined plasma MMP-9 levels at baseline and after three months of randomisation to either placebo (n=202) or fosinopril (20 mg/day, n=204) treatment. RESULTS: Baseline plasma MMP-9 levels were not related to baseline UAE (r=-0.008, p=0.871). Three months of fosinopril treatment effectively reduced UAE compared to placebo treatment (-10.4+/-2.4 vs. 1.8+/-1.3 mg/24 hours, p<0.001, respectively). However, fosinopril treatment failed to significantly change plasma MMP-9 levels compared to placebo (-0.47+/-7.68 vs. 0.06+/-9.20, p=0.646, respectively). In addition, the change in UAE was not related with change in MMP-9 levels. CONCLUSION: The effective reduction of UAE with fosinopril was not related to plasma MMP-9 levels.     

The Acute Effects of FK-506 on Renal Haemodynamics,Water and Sodium Excretion and Plasma Levels of Angiotensin II,Aldosterone, Atrial Natriuretic Peptide and Vasopressin in Pigs

FK-506 has been shown to be an effective immunosuppressive drug with possible nephrotoxic side effects. In this study we have investigated the acute effects of FK-506 on renal haemodynamics, water, sodium and lithium excretion rates and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and vasopressin in 29 anaesthetized Lancaster/Yorkshire female pigs. A continuous intravenous infusion was given over a 2-h period to 4 groups: A: 0.075 mg kg^?1 (n = 7), B: 0.15 mg kg^?1 (n = 8), C: 0.3 mg kg^?1 (n = 6) and P: placebo vehicle (n = 8). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion clearance technique using 125-I-iothalamate and 131-I-hippuran as reference substances. Hormonal parameters were measured by radioimmunoassay. In all three FK-506 groups, fractional lithium excretion was significantly decreased 2 h after FK506 infusion (P: + 0.4%, A: ? 8.8% (P < 0.05), B: ?12.9% and C: ?11.2% (P < 001 for both). Mean arterial blood pressure (MBP) was significantly increased in the two highest dosage groups (B,C) at 2 h of infusion: (MBP; P: +2.9%, A: +3.5%, B: +12.0%, C: + 15.3% (P < 0.01 for both). GFR and RPF showed minor and inconsistent changes while all other parameters measured showed similar or no changes. In conclusion, acute infusion of FK-506 to pigs does not change overall renal function significantly, but increases mean arterial blood pressure and decreases fractional excretion of lithium.     

Long-term effects of diltiazem and atenolol on blood glucose, serum lipids, and serum urate in hypertensive patients. Swedish-Finnish Study Group

The purpose of this long-term treatment study was to evaluate health-related quality of life by comparing the effects of diltiazem and atenolol on some important metabolic parameters. SUBJECTS, MATERIAL AND METHODS: In a Swedish-Finnish long-term multicenter study 256 patients with mild to moderate hypertension were randomized to treatment with diltiazem retard (D) (n = 127) or atenolol (A) (n = 129). Doses could be increased and additional captopril medication be given to achieve adequate blood pressure (BP) reduction. The treatment in group D lasted for two years while group A was treated for 1 year and then was given D for another 2 years. RESULTS: After 1 year BP was significantly reduced in both groups and to a similar degree. The BP reduction was maintained during the rest of the study. After 1 and 2 years, HDL had increased significantly (p < 0.001) in group D. There was a corresponding significant reduction of the LDL/HDL ratio. In group A there were no changes after 1 year regarding lipoprotein levels. After the switch to D, group A showed similar improvements regarding HDL and the LDL/HDL ratio as the original D group. CONCLUSION: It is concluded that D and A are equally effective in lowering BP. However, long-term treatment with D, but not with A, has a favorable effect on HDL concentrations and the LDL/HDL ratio. According to these findings D affects the risk factor profile in hypertension.     

Effect of imidapril versus ramipril on urinary albumin excretion in hypertensive patients with type 2 diabetes and microalbuminuria

Objective: Aim of this study was to compare the antiproteinuric effect of imidapril (I) and ramipril (R) in diabetic hypertensive patients with microalbuminuria.

Research design and methods: One hundred and seventy-six patients were randomised to I 10 – 20 mg once daily (od) (n = 88) or R 5 – 10 mg od (n = 88) for 24 weeks. Clinic, ambulatory, central blood pressure (BP), urinary albumin excretion (UAE), plasma Angiotensin II (Ang II), bradykinin and brain natriuretic peptide (BNP) were assessed at baseline and after 6, 12 and 24 weeks.

Results: Both I and R produced a similar decrease in clinic, ambulatory and central BP (p < 0.001 vs baseline). Both treatments significantly reduced UAE throughout the study, but the decrease in UAE associated with I was more pronounced, being evident at week 6 (p = 0.05) and maximal at week 24 end-point (?42 vs –29%, p < 0.01). BNP and Ang II levels were similarly reduced by I and R, while bradykinin increased more with R (+132 vs +86%, p < 0.05).

Conclusions: These findings showed that in diabetic hypertensive patients with microalbuminuria, despite equivalent BP-lowering effect, I produced a greater antiproteinuric effect than R, which might be due to different intrinsic molecular properties of the two drugs.     

Suboptimal choices and dosing of statins at start of therapy

AIM: To assess dosing and determinants of the choice of statins among starters of statins. METHODS: Data were obtained from the PHARMO database comprising pharmacy and linked hospital discharge records of approximately 300 000 subjects in the Netherlands. All new users of statins in 1998 were selected. Patient characteristics and drug regimens were compared between starters of different statins. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using polytomous logistic regression modelling, using the start of simvastatin therapy as reference category. RESULTS: In 1998, 1738 patients started using simvastatin (41.1%), pravastatin (23.1%), fluvastatin (11.9%), atorvastatin (22.8%) or cerivastatin (1.0%). Compared with starters with simvastatin [mean dose 1.02 +/- 0.39 defined daily doses (DDDs)], starters with pravastatin (1.27 +/- 0.56 DDDs) and atorvastatin (1.43 +/- 0.59 DDDs) received higher doses (P < 0.001), whereas users of fluvastatin (0.78 +/- 0.37 DDDs) and cerivastatin (0.81 +/- 0.30 DDDs) received lower doses (P < 0.001). Patients already using CYP3A4 inhibitors more frequently received fluvastatin (OR = 1.80; 95% CI 1.11, 2.94), metabolized by non-CYP3A4 pathways, and atorvastatin (OR = 1.62; 95% CI 1.06, 2.47), which is metabolized by CYP3A4, than simvastatin. Statin doses were not adjusted when prescribed to patients using CYP3A4 inhibitors. CONCLUSIONS: Many patients starting statin therapy did not receive a statin of first choice. The coadministration of potentially interacting drugs may have led to a change in statin choice, but not in dosage lowering. These findings suggest that the quality of statin therapy could be improved.     

Pressor responses to hyperventilation in elderly subjects differentiate essential from secondary hypertension

We evaluated pressor responses to the hyperventilation test in elderly normotensive (n=43, mean age 82 ± 5 years) and elderly hypertensive subjects (n=45 with essential hypertension, mean age 82 ± 2 years, and n=49 with secondary hypertension, mean age 82 ± 3 years). Hyperventilation did not change blood pressure (BP) in normotensive and secondary hypertensive subjects, whereas it decreased BP in essential hypertensives. Hierarchical cluster analysis based on BP responses to hyperventilation disclosed three groups of subjects in each population: group 1 exhibited a reduction in BP (essential hypertensives: 76%), group 2 no change (normotensives: 70%, secondary hypertensives: 76%), and group 3 an increase (normotensives: 19%, essential hypertensives: 13%, secondary hypertensives: 14%). Ambulatory BP monitoring found significant differences in pressor daytime profiles of hypertensive patients according to pressor responses to hyperventilation showing wide fluctuations in group 1 and 3 patients. Interestingly, the peak ambulatory SBP values correlated to the pre-hyperventilation SBP values in group 1, and to the hyperventilation peak SBP values in group 3. In conclusion: 1) Aging decreases reactivity to respiratory alkalosis in elderly normotensives; 2) hyperventilation induces significant pressor changes frequently in essential hypertension, but rarely in secondary hypertension; 3) the significant pressor responses to hyperventilation reflect the daytime pressor profiles predicting the highest daily fluctuations of BP values.     

The trade-off between cardiovascular and gastrointestinal effects of rofecoxib

BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.     

贝那普利对老年糖尿病肾病早期尿微量白蛋白排泄率的影响

目的　研究贝那普利对老年糖尿病肾病 (DN)早期尿微量白蛋白排泄率 (UAE)及肾功能的影响。方法　 6 3例随机分为治疗组和对照组 ,治疗组 33例予贝那普利 5～ 10mg ,qd ,口服 ;对照组 30例予哌唑嗪 0 5～ 1mg ,bid ,口服。观察治疗前、后 2 4hUAE、肾小球滤过率 (GFR)、平均动脉压 (MAP)变化。 结果　治疗组UAE显著减少 (P <0 0 1) ,肾小球高滤过恢复正常 ,并明显优于对照组 (P <0 0 1)。两组治疗后平均动脉压均降至正常。结论　贝那普利在有效降低动脉血压同时具有明显减少早期尿微量白蛋白作用 ,提示对肾脏有保护作用。